Modulation of the Liver–Brain Axis by Ondansetron in Thio-Acetamide-Induced Acute Hepatic Encephalopathy
8 affiliations
- 1Department of Emergency Medicine, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan 24100, Türkiye
- 2Department of Physiology, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan 24100, Türkiye
- 3Department of Emergency Medicine, Mengücek Gazi Training and Research Hospital, Erzincan 24100, Türkiye
- 4Department of Pathology, Faculty of Veterinary Medicine, Cumhuriyet University, Sivas 58140, Türkiye
- 5Laboratory Technician and Veterinary Health Program, Health Services Vocational School, Osmaniye Korkut Ata University, Osmaniye 80000, Türkiye
- 6Department of Biochemistry, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan 24100, Türkiye
- 7R&D Activities and Research Laboratories, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan 24100, Türkiye
- 8Department of Pharmacology, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan 24100, Türkiye
Abstract
Hepatic encephalopathy (HE) is a severe neurological complication of liver failure characterized by hyperammonemia, oxidative stress, neuroinflammation, and progressive neuronal dysfunction. Ondansetron (OND), a selective 5-hydroxytryptamine-3 (5-HT3) receptor antagonist, has reported anti-inflammatory and neuroactive properties, but its effects in HE remain poorly defined. This study evaluated OND in a thioacetamide (TAA)-induced acute HE model in female Sprague-Dawley rats. Animals were assigned to Control, TAA, OND, TAA+OND (0.5 mg/kg), and TAA+OND (1 mg/kg) groups. Serum and cerebral glutamine, oxidative and antioxidant parameters, histopathological alterations, and TLR2, NF-κB, IL-1β, GFAP, NLRP3, and caspase-1 immunoreactivity were assessed in liver and brain tissues. TAA increased glutamine accumulation, produced tissue injury, altered redox parameters, and increased several inflammation-related markers. OND significantly reduced cerebral glutamine and attenuated selected biochemical, histopathological, and immunohistochemical alterations, with generally more pronounced effects at 0.5 mg/kg. These findings indicate that OND administration is associated with partial modulation of metabolic, oxidative, inflammatory, and structural alterations in TAA-treated rats, warranting further receptor-specific and functional studies to clarify its mechanisms and therapeutic relevance.
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BibTeX
@article{sari2026modulation,
title = {{Modulation of the Liver–Brain Axis by Ondansetron in Thio-Acetamide-Induced Acute Hepatic Encephalopathy}},
author = {Fatih Mehmet Sari and Yasin Bilgin and Betul Cicek and Engin Kurt and Mustafa Ozkaraca and Ali Gungor and Nezahat Kurt and Asli Ozbek Bilgin},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209265},
url = {https://www.mdpi.com/1422-0067/27/20/9265},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Modulation of the Liver–Brain Axis by Ondansetron in Thio-Acetamide-Induced Acute Hepatic Encephalopathy
AU - Fatih Mehmet Sari
AU - Yasin Bilgin
AU - Betul Cicek
AU - Engin Kurt
AU - Mustafa Ozkaraca
AU - Ali Gungor
AU - Nezahat Kurt
AU - Asli Ozbek Bilgin
PY - 2026
DA - 2026/10/19
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209265
UR - https://www.mdpi.com/1422-0067/27/20/9265
AB - Hepatic encephalopathy (HE) is a severe neurological complication of liver failure characterized by hyperammonemia, oxidative stress, neuroinflammation, and progressive neuronal dysfunction. Ondansetron (OND), a selective 5-hydroxytryptamine-3 (5-HT3) receptor antagonist, has reported anti-inflammatory and neuroactive properties, but its effects in HE remain poorly defined. This study evaluated OND in a thioacetamide (TAA)-induced acute HE model in female Sprague-Dawley rats. Animals were assigned to Control, TAA, OND, TAA+OND (0.5 mg/kg), and TAA+OND (1 mg/kg) groups. Serum and cerebral glutamine, oxidative and antioxidant parameters, histopathological alterations, and TLR2, NF-κB, IL-1β, GFAP, NLRP3, and caspase-1 immunoreactivity were assessed in liver and brain tissues. TAA increased glutamine accumulation, produced tissue injury, altered redox parameters, and increased several inflammation-related markers. OND significantly reduced cerebral glutamine and attenuated selected biochemical, histopathological, and immunohistochemical alterations, with generally more pronounced effects at 0.5 mg/kg. These findings indicate that OND administration is associated with partial modulation of metabolic, oxidative, inflammatory, and structural alterations in TAA-treated rats, warranting further receptor-specific and functional studies to clarify its mechanisms and therapeutic relevance.
SN - 1422-0067
ER -